Changes in antidepressant use by young people and suicidal behavior after FDA warnings and media coverage: quasi-experimental study

Re: Changes in antidepressant use by young people and suicidal behavior after FDA warnings and media coverage: quasi-experimental study

In their recent article, Dr. Lu and colleagues hypothesize that the US Food and Drug Administration (FDA) 2003 safety warnings regarding antidepressants reduced antidepressant prescribing and thereby increased suicide attempts in young people (1). To test this hypothesis, they offer an ecological analysis of health care claims data from three age groups. They focus on associations between trends before and after the FDA’s action in the fraction of the population receiving antidepressants, on the one hand; and the suicide attempt rate, as measured by psychotropic poisonings observed in emergency department visits and hospital admissions, on the other. They conclude that the FDA warnings were associated with significant declines in the fraction of each age group receiving antidepressants and with increases in suicide attempts among young people. We question whether the data support these conclusions.

Most importantly, we doubt psychotropic poisonings (ICD-9 code 969) are a “validated proxy for suicide attempts.” Most suicide attempts in young people do not involve poisoning by psychotropic drugs; and most poisoning events with psychotropic drugs, which include caffeine, stimulants, benzodiazepines, hallucinogens, and several other agents, are not suicide attempts.

Only a small minority of suicide attempts in young people involve psychotropic intoxications. Among young people in the United States ages 10-24 years, approximately 45% of non-fatal intentional injuries are related to poisonings of any kind (2). Most intentional poisoning events in turn involve alcohol (62%) and illicit drugs (34%) rather than prescribed pharmaceuticals (13%), only some of which are psychotropic medications (3). Moreover, because only a small minority of youth receive any treatment following suicide attempts (4), a narrow focus on acute care visits for psychotropic drug poisoning is clearly an unreliable measure of suicide attempts.

Although intoxication from psychotropic agents is often intentional rather than accidental, most such intoxications do not represent suicide attempts. Across all ages, approximately one-half (52.4%) of emergency visits for psychotropic medication intoxication are intentional (5). In community and acute care settings, however, a substantial proportion of young people who engage in deliberate self-harm report either no intent to die (6) or low levels (7) of suicidal intent. Although the authors cite a prior study to assert that the positive predictive value (PPV) for psychotropic drug poisoning is 79.7% for deliberate self-harm, the actual PPV in their sample is likely much lower, because the cited PPV figure is based on a highly enriched sample with a drug poisoning rate (3.32%) (8) that is over 100 times greater than in the present samples (0.01% to 0.02%).

Evidence on changes in antidepressant use after the FDA warning is also complex. The large “declines” the authors report are relative to forward projection of trends prior to the FDA warning, when antidepressant use had been increasing year to year. In absolute terms, however, the authors find only a modest decrease in the fraction of children and adolescents receiving antidepressants, and essentially no change in the fraction of young adults and adults. Yet the hypothesis of increases in suicidality is premised on absolute declines in antidepressant use, not declines relative to a hypothetical projection.

A more plausible explanation for the reported findings, which is consistent with prior research (9), is that the FDA warnings slowed prior growth in the rate of antidepressant treatment. In the following years, there was substantial – but likely unrelated – increase in emergency department visits and hospital admissions by young people in the United States related to the non-medical use of benzodiazepines (10), stimulants (11), and other psychotropic agents. Poisonings represent one aspect of this broader trend. Unintentional poisonings from stimulants and other ADHD medications, for example, increased roughly three fold between 2000-2002 and 2009-2010 (12). The societal factors that have driven the increase in nonmedical use and unintentional intoxications merit further study.

Dr. Lu and colleagues raise important questions concerning the complex relationships between anxiety and depressive disorders, antidepressant treatment, and the risk of self-harm and suicide. One promising approach to these elusive associations may involve population-based cohort studies that draw on the impressive power available in claims and electronic health records. Mandating use of E-codes to capture deliberate self-harm and developing coding schemes to distinguish suicidal and non-suicidal intent would offer critical scaffolding on which to build such research.

Disclaimer: This letter does not necessarily reflect the opinions of the National Institute of Mental Health, the Department of Health and Human Services, or the US federal government. The authors have read and understood BMJ policy on declaration of interests and declare that they have no competing interests.